Abnormal neutrophil chemotactic activity in children with congenital insensitivity to pain with anhidrosis (CIPA): the role of nerve growth factor.
A 1926-ins-T mutation in the TrkA gene encoding the tyrosine kinase receptor for nerve growth factor (NGF) was previously documented in patients with congenital insensitivity to pain with anhidrosis (CIPA). These patients suffer from skin lacerations which often evolve into deep tissue infections. Abnormality in neutrophil functions may explain this high rate of severe infections. In this study we show that chemotaxis was significantly (P<0.001) suppressed in patients' neutrophils, compared to healthy controls. Although NGF alone did not exert a chemotactic effect, its presence enhanced both migration toward fMLP and phosphorylation of MAP kinases (ERK and JNK) in neutrophils from healthy controls, but not in neutrophils from CIPA patients. The significantly impaired chemotactic activity of neutrophils from a CIPA patient, which has been attributed to the molecular defect in the TrkA receptor, may contribute to the high rate of infection.
Beigelman
Avraham
A
Department of Pediatrics, Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, 84101, Israel.
Levy
Jacov
J
Hadad
Nurit
N
Pinsk
Vered
V
Haim
Alon
A
Fruchtman
Yariv
Y
Levy
Rachel
R
D000293:Adolescent; D000328:Adult; D018925:Chemokines / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D007007:Hypohidrosis / Q000150:complications*; D007223:Infant; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020932:Nerve Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism*; D000699:Pain Insensitivity, Congenital / Q000150:complications* / Q000276:immunology / Q000503:physiopathology*; D055815:Young Adult
D018925:Chemokines; D020932:Nerve Growth Factor; D048052:Mitogen-Activated Protein Kinase 3; D048670:MAP Kinase Kinase 4